Percutaneous transluminal angioplasty (PTA), defined as any percutaneous transluminal method of decreasing stenosis within a blood vessel, whether caused by the existence of an atheromatous plaque, thrombosis, embolus, and/or mineral deposit, by any of a number of means such as balloon dilatation, thermal ablation, laser atherectomy, mechanical shaving, extraction, or ultrasonic pulverization, hereinafter referred to as angioplasty, is widely used in the treatment of occlusive vascular disease. However, it has been found that restenosis frequently occurs, and in the case of coronary angioplasty, restenosis occurs in about a third of cases within 6 months of the procedure.
Sahni, R., et al, "Prevention of Restenosis by Lovastatin," 62nd Scientific Sessions of the American Heart Association, New Orleans, Nov. 13-16 1989, Circulation 80 (4 Suppl. 2) 1989, p. II-65, disclose that lovastatin significantly reduces the incidence of restenosis following successful PTCA.
Gellman, J., et al, "Lovastatin, a HMG CoA Reductase Inhibitor, Reduces Restenosis Following Balloon Angioplasty in an Atherosclerotic Hypercholesterolemic Rabbit," Clinical Research, Vol. 37, No. 2, 1989, p. 261A, disclose that "lovastatin reduces total cholesterol and retards restenosis following balloon angioplasty in the hypercholesterolemic rabbit and merits evaluation in patients."
Pravastatin, also referred to as CS-514, an HMG CoA reducase inhibitor, is disclosed in U.S. Pat. No. 4,346,227.
European Patent Application 0219782 to Scholkens (Hoechst) discloses the treatment of atherosclerosis, thrombosis and/or peripheral vascular disease in mammals using an angiotensin converting enzyme (ACE) inhibitor or its physiologically tolerable salts. It further discloses that because ACE is predominantly localized in the luminal plasma membrane of the endothelial cell, ACE inhibitors can interfere in platelet-endothelium interaction. In addition, Scholkens discloses that ACE inhibition potentiates the action of bradykinin (a strong stimulator of prostacyclin release from endothelial cells) by inhibiting its degradation and ACE inhibitors, consequently, have an inhibitory effect on platelet aggregation.
Powell, J.S. et al "Inhibitors of Angiotension-Converting Enzyme Prevent Myointimal Proliferation After Vascular Injury," Science, Vol. 245, 186-188, Jul. 14, 1989, disclose that angiotensin-converting enzyme may participate in modulating the proliferative response of the vascular wall after arterial injury, and inhibition of this enzyme may have therapeutic applications to prevent the proliferative lesions that occur after coronary angioplasty and vascular surgery.
Other references which indicate that ACE inhibitors may prevent restenosis following angioplasty include "AII is Mitogenic for Endothelial Cells" (Clin. Res. 36, 1988:259A); "Exposure of Smooth Muscle Cells to AII Results in Expression of the Proto-Oncogene for PDGF" (J. Clin. Invest. 83, 1989:1419); "Cilazapril (and Captopril) Reduces the Myointimal Proliferation (Restenosis) in Rat Carotids Subjected to Balloon Angioplasty" (Clin. Res. 37, 1989:286A).
U.S. Pat. Nos. 4,046,889 and 4,105,776 to Ondetti et al disclose proline derivatives, including captopril, which are angiotensin converting enzyme (ACE) inhibitors useful for treating hypertension.
U.S. Pat. No. 4,337,201 to Petrillo discloses phosphinylalkanoyl substituted prolines, including fosinopril, which are ACE inhibitors useful for treating hypertension.
U.S. Pat. No. 4,374,829 discloses carboxyalkyl dipeptide derivatives, including enalapril, which are ACE inhibitors useful for treating hypertension.
U.S. Pat. No. 4,452,790 to Karanewsky et al discloses phosphonate substituted amino or imino acids and salts thereof and covers (S)-1-[6-amino-2-[hydroxy(4-phenylbutyl)phosphinyl]oxy]-1-oxohexyl]-L-prol ine (SQ 29,852, ceranapril). These compounds are ACE inhibitors useful in treating hypertension.
U.S. Pat. No. 4,316,906 to Ondetti et al discloses ether and thioether mercaptoacyl prolines which are ACE inhibitors useful in treating hypertension. This Ondetti et al patent covers zofenopril.